Cryptosporidium spp. was once thought to be a commensal organism. However, in 1955 the organism was associated with turkey enteritis. Florence G. Crawford, "Human Cryptosporidiosis," CRC Critical Reviews and Microbiol., 16(2) :113-159, 113 (1988). The organism was later found to be a bovine pathogen in 1971 and a human pathogen in 1976. Id. Cryptosporidium spp. is now recognized as an important enteric protozoan pathogen, most commonly identified in cases of acute, self-limiting diarrheal diseases in poultry and mammals. Edward N. Janoff et al., "Cryptosporidium Species, a Protean Protozoan," J. Clin. Microbiol. 25(6):967-975, 970 (June 1987). The specie which causes disease in humans is believed to be C. parvum. Id. at 113.
In cattle, Cryptosporidium is most commonly seen in calves less than three weeks old. "Cryptosporidiosis," in Current Veterinary Therapy: Food Animal Practice, 779, (Jimmy L. Howard ed. 1990). The disease is accompanied by anorexia, dehydration, weight loss, debility and occasionally death. Id.
Although the precise prevalence of Cryptosporidium in humans is unknown, it is recognized worldwide as a common cause of enteritis. Rosemary Soave et al., "Cryptosporidium and Other Protozoa Including Isospora, Sarcocystis, Balantidium coli and Blastocystis," in Principles and Practice of Infectious Diseases 235, (Gerald L. Mandel et al., eds., 1990). The organism is commonly found in immunocompetent patients showing clinical symptoms of diarrhea. Janoff at 967. Symptoms in humans include diarrhea, abdominal pain, cramping, vomiting, anorexia, malaise and weight loss and may include death in young children and aged adults. Id. at 971. The pathogenesis of human Cryptosporidium is not completely known. Crawford at 145; Janoff at 970.
The Cryptosporidium organism is also found in immunocompromised individuals. Today, many cases of Cryptosporidium in immunocompromised individuals are in persons suffering from acquired immunodeficiency syndrome (AIDS). In one study, the most common pathogen associated with diarrhea in AIDS patients was Cryptosporidium. Barbara E. Laughon et al., "Prevalence of Enteric Pathogens in Homosexual Men With and Without Acquired Immunodeficiency Syndrome," Gastroenterology 94(4):984-992, 984 (April 1988). Moreover, unlike the symptoms seen in immunocompetent patients, the syndrome in immunocompromised individuals may be of greater severity and may persist for many months causing anorexia, abdominal pain, weight loss, vomiting, diarrhea, malaise, low-grade fever, and even death due to dehydration and cachexia. Janoff at 971. In addition, occasional coughing and progressive pulmonary disease are seen. Id. at 971.
Therefore, as seen in immunocompromised individuals, Cryptosporidium is not necessarily self-limiting. Id. In fact, CDC sources have reported that cumulative case fatality rates through April 1986 were significantly higher in AIDS patients affected by Cryptosporidium. Crawford at 132. Moreover, it is believed that AIDS patients who recover from clinical cryptosporidiosis still harbor low levels of Cryptosporidium oocysts. Id.
In humans, treatment of Cryptosporidium using single and multiple-drug regimens has, at best, met with limited success. Janoff at 972; Crawford at 147; K. W. Angus, "Cryptosporidiosis and AIDS," Bailliere's Clinical Gastroenterology 4(2):425-441, 435 (June 1990). And, while immunoprophylaxis has been suggested, a Cryptosporidium vaccine capable of producing immune stimulation has not been described. Id. at 436-37.
The use of adjuvants to enhance in vitro immune stimulation against various organisms is well known. Adjuvants known in the art include, for example, alum, aluminum hydroxide, aluminum phosphate and water-in-oil emulsions. In addition, prior art adjuvants may include components of microorganisms as immuno-stimulants, for example, Freund's-complete-adjuvant is a water-in-oil adjuvant which also contains dead Mycobacteria. Other species of bacteria are also known to enhance the immune response of a human or animal, for example, Nocardia, Bordetella and Corynebacterium parvum.
The use of Candida spp. antigens to stimulate specific immunity to the Candida organism is known in the art. However, the use of Candida antigens as an adjuvant material to enhance the in vitro immune response to antigens other than Candida has not previously been described.